tbuckley/cabot-search huggingface dataset:
Promising role of protein arginine methyltransferases in overcoming anti-cancer drug resistance
Authors: Yongxia Zhu, Tong Xia, Da-Qian Chen, Xia Xiong, Lihong Shi, Yueqi Zuo, Hongtao Xiao, Li Liu
Journal: Drug Resistance Updates (2023)

Drug resistance remains a major challenge in cancer treatment, necessitating the development of novel strategies to overcome it. Protein arginine methyltransferases (PRMTs) are enzymes responsible for epigenetic arginine methylation, which regulates various biological and pathological processes, as a result, they are attractive therapeutic targets for overcoming anti-cancer drug resistance. The ongoing development of small molecules targeting PRMTs has resulted in the generation of chemical probes for modulating most PRMTs and facilitated clinical treatment for the most advanced oncology targets, including PRMT1 and PRMT5. In this review, we summarize various mechanisms underlying protein arginine methylation and the roles of specific PRMTs in driving cancer drug resistance. Furthermore, we highlight the potential clinical implications of PRMT inhibitors in decreasing cancer drug resistance. PRMTs promote the formation and maintenance of drug-tolerant cells via several mechanisms, including altered drug efflux transporters, autophagy, DNA damage repair, cancer stem cell-related function, epithelial-mesenchymal transition, and disordered tumor microenvironment. Multiple preclinical and ongoing clinical trials have demonstrated that PRMT inhibitors, particularly PRMT5 inhibitors, can sensitize cancer cells to various anti-cancer drugs, including chemotherapeutic, targeted therapeutic, and immunotherapeutic agents. Combining PRMT inhibitors with existing anti-cancer strategies will be a promising approach for overcoming anti-cancer drug resistance. Furthermore, enhanced knowledge of the complex functions of arginine methylation and PRMTs in drug resistance will guide the future development of PRMT inhibitors and may help identify new clinical indications.
Publisher Correction: Adjuvant nivolumab in resected stage IIB/C melanoma: primary results from the randomized, phase 3 CheckMate 76K trial
Authors: John M. Kirkwood, Michele Del Vecchio, Jeffrey Weber, Christoph Hoeller, Jean-Jacques Grob, Peter Mohr, Carmen Loquai, Caroline Dutriaux, Vanna Chiarion-Sileni, Jacek Mackiewicz, Piotr Rutkowski, Petr Arenberger, Gaelle Quereux, Tarek M. Meniawy, Paolo A. Ascierto, Alexander M. Menzies, Piyush Durani, Maurice Lobo, Federico Campigotto, Brian Gastman, Georgina V. Long
Journal: Nature Medicine (2023)
Gasdermin D permeabilization of mitochondrial inner and outer membranes accelerates and enhances pyroptosis
Authors: Rui Miao, Cong Jiang, Winston Y. Chang, Haiwei Zhang, Jinsu An, Felicia Ho, Pengcheng Chen, Han Zhang, Caroline Junqueira, Dulguun Amgalan, Felix G. Liang, Junbing Zhang, Charles L. Evavold, Iva Hafner-Bratkovič, Zhibin Zhang, Pietro Fontana, Shiyu Xia, Markus Waldeck-Weiermair, Youdong Pan, Thomas Michel, Liron Bar-Peled, Hao Wu, Jonathan C. Kagan, Richard N. Kitsis, Peng Zhang, Xing Liu, Judy Lieberman
Journal: Immunity (2023)
Equity and technology in the pandemic treaty
Authors: Matthew M Kavanagh, Luis Gil Abinader, Amanda Banda
Journal: BMJ (2023)

Within a year of the first reported covid-19 cases, effective vaccines were approved in Europe and North America using technology that would win the Nobel prize. 1 2 Yet just 1% of all vaccines produced in the first year went to low income countries. 3Much the same happened in the early years of HIV treatment.Breakthrough antiretroviral therapy slashed mortality in high income countries, but drugs were priced out of reach for people in Africa, Asia, and Latin America until intellectual property and production barriers were overcome and generic versions arrived. 4In both cases, remarkable scientific victory was undermined by similarly remarkable equity failure.The pandemics were prolonged, took many more lives, and had highly unequal impacts because of inequitable distribution.
Long COVID: a new word for naming fibromyalgia?
Authors: Xavier Mariette
Journal: Annals of the Rheumatic Diseases (2023)

Long COVID is the name given to a syndrome comprising a wide variety of symptoms persisting more than 3 months after acute benign COVID-19, with a prevalence ranging from 10 to 80%. Symptoms are very close to fibromyalgia. Several studies showed that long COVID prevalence was much higher after the first wave of the pandemics and was associated to the fact of thinking having had COVID rather than having had really COVID. Thus, it was the stress of the first wave with the lockdown and not the consequences of the infection that probably induced this high frequency of long COVID. Numbers of studies tried to find objective biological abnormalities for explaining long COVID but none of them could be replicated and convincing. The concept of long COVID seems to be a repetition of history of medicine, in which the doctors and the society gave different names to fibromyalgia with the objective of trying to highlight the fact that fibromyalgia could be a somatic disease with a well understood pathophysiology and to avoid to focus on the psychosomatic aspects of the disease. In conclusion, “to name is to soothe” as said by Roland Barthes. However, “Naming things wrongly adds to the world's unhappiness” was saying Albert Camus. Thus, the term of long COVID, which suggests viral persistence of impaired immune response to the virus, is unappropriated and should be replaced by fibromyalgia-like post-COVID syndrome. Research on the psychosomatic and somatic mechanisms involved in these fibromyalgia-like post-viral syndromes must be encouraged.
Selectivity, efficacy and safety of JAKinibs: new evidence for a still evolving story
Authors: Michael Bonelli, Andreas Kerschbaumer, Kastriot Kastrati, Kamran Ghoreschi, Massimo Gadina, Leonhard X Heinz, Josef S Smolen, Daniel Aletaha, John O’Shea, Arian Laurence
Journal: Annals of the Rheumatic Diseases (2023)

Fundamental insight gained over the last decades led to the discovery of cytokines as pivotal drivers of inflammatory diseases such as rheumatoid arthritis, psoriasis/psoriasis arthritis, inflammatory bowel diseases, atopic dermatitis and spondylarthritis. A deeper understanding of the pro-inflammatory and anti-inflammatory effects of various cytokines has prompted new cytokine-targeting therapies, which revolutionised the treatment options in the last years for patients with inflammatory disorders. Disease-associated immune responses typically involve a complex interplay of multiple cytokines. Therefore, blockade of one single cytokine does not necessarily lead to a persistent remission in all patients with inflammatory disorders and fostered new therapeutic strategies targeting intracellular pathways shared by multiple cytokines. By inhibiting JAK-STAT signalling pathways common to families of cytokines, JAK-inhibitors (JAKinibs) have created a new paradigm for the treatment of inflammatory diseases. Multiple agents have been approved for various disorders and more are being investigated for several new indications. Second-generation selective JAKinibs have been devised with the aim to achieve an increased selectivity and a possible reduced risk of side effects. In the current review, we will summarise the current body of evidence of pan versus selective JAKinibs and the most recent insights on new side effects and indications, including COVID-19.
Effectiveness of BNT162b2 mRNA vaccine third doses and previous infection in protecting against SARS-CoV-2 infections during the Delta and Omicron variant waves; the UK SIREN cohort study September 2021 to February 2022
Authors: Victoria J. Hall, Ferdinando Insalata, Sarah Foulkes, Peter Kirwan, Dominic Sparkes, Ana Atti, Michelle Cole, Elen de Lacy, Lesley Price, Diane Corrigan, Colin S. Brown, Jasmin Islam, Andre Charlett, Susan Hopkins
Journal: Journal of Infection (2023)

Third doses of COVID-19 vaccines were widely deployed following the primary vaccine course waning and the emergence of the Omicron-variant. We investigated protection from third-dose vaccines and previous infection against SARS-CoV-2 infection during Delta-variant and Omicron-variant (BA.1 & BA.2) waves in our frequently PCR-tested cohort of healthcare-workers. Relative effectiveness of BNT162b2 third doses and infection-acquired immunity was assessed by comparing the time to PCR-confirmed infection in boosted participants with those with waned dose-2 protection (≥254 days after dose-2), by primary series vaccination type. Follow-up time was divided by dominant circulating variant: Delta 07 September 2021 to 30 November 2021, Omicron 13 December 2021t o 28 February 2022. We used a Cox regression model with adjustment/stratification for demographic characteristics and staff-type. We explored protection associated with vaccination, infection and both. We included 19,614 participants, 29% previously infected. There were 278 primary infections (4 per 10,000 person-days of follow-up) and 85 reinfections (0.8/10,000 person-days) during the Delta period and 2467 primary infections (43/10,000 person-days) and 881 reinfections (33/10,000) during the Omicron period. Relative Vaccine Effectiveness (VE) 0-2 months post-3rd dose (3rd dose) (3-doses BNT162b2) in the previously uninfected cohort against Delta infections was 63% (95% Confidence Interval (CI) 40%-77%) and was lower (35%) against Omicron infection (95% CI 21%-47%). The relative VE of 3rd dose (heterologous BNT162b2) was greater for primary course ChAdOX1 recipients, with VE 0-2 months post-3rd dose over ≥68% higher for both variants. Third-dose protection waned rapidly against Omicron, with no significant difference between two and three BNT162b2 doses observed after 4-months. Previous infection continued to provide additional protection against Omicron (67% (CI 56%-75%) 3-6 months post-infection), but this waned to about 25% after 9-months, approximately three times lower than against Delta. Infection rates surged with Omicron emergence. Third doses of BNT162b2 vaccine provided short-term protection, with rapid waning against Omicron infections. Protection associated with infections incurred before Omicron was markedly diminished against the Omicron wave. Our findings demonstrate the complexity of an evolving pandemic with the potential emergence of immune-escape variants and the importance of continued monitoring.
Preliminary summary and reclassification of cases from the Pediatric Research of Management in Stevens-Johnson syndrome and Epidermonecrolysis (PROMISE) study: A North American, multisite retrospective cohort
Authors: Sylvia Martinez-Cabriales, Jerome Coulombe, Michelle Aaron, Sadaf H. Hussain, Danny Linggonegoro, Irene Lara-Corrales, Hailey Barootes, Heather Brandling-Bennett, Isabela Covelli, Anna Yasmine Kirkorian, Nidhi Shah, Leslie Castelo-Soccio, Paige McKenzie, Lisa M. Arkin, Adam Heinze, Carmen Liy-Wong, Nicole Travis, Michael Rieder, Blanca R. Del Pozzo-Magana, Jennifer J. Schoch, Reesa Monir, Sharon A. Glick, Laura Uwakwe, Sarah Skillman, Dan P. Hekman, Brendan C. Lethebe, Michele L. Ramien
Journal: Journal of the American Academy of Dermatology (2023)
Use of simple endoscopic ligation to successfully remove a large torsional colonic lipoma causing intussusception
Authors: Yadi Lan, Shulei Zhao, Hongwei Xu
Journal: Endoscopy (2023)

Colonic lipomas are uncommon benign submucosal tumors that are usually asymptomatic. However, some lipomas >4 cm may cause intussusception, abdominal pain, or hematochezia [1]. Most patients with giant lipomas require surgery for relief of symptoms [2]. Recently, endoscopic mucosal resection, endoscopic mucosal resection after precutting, and endoscopic submucosal dissection have been reported for the treatment of large lipomas [3]. However, the fatty tissue is an inefficient conductor of electronic current and may lead to a high incidence of complications [4]. We report the use of endoscopic ligation for the treatment of a large, torsional, colonic lipoma causing intussusception.
Positive fecal immunochemical test but negative colonoscopy: what’s next?
Authors: Nastazja Pilonis
Journal: Endoscopy (2023)

Screening for colorectal cancer (CRC) using the fecal immunochemical test (FIT) has been rapidly implemented worldwide. Alongside primary colonoscopy, it is a first-tier recommended screening test. FIT testing offers several advantages, including noninvasiveness, high acceptance among the target population, and cost-effectiveness [1] [2] [3]. However, it is not without challenges, particularly concerning the management of individuals with a negative colonoscopy following a positive FIT result.
What is a psychopathology dimension?
Authors: Christopher J. Hopwood, Leslie C. Morey, Kristian E. Markon
Journal: Clinical Psychology Review (2023)

Coherence in the science and practice of mental health assessment depends upon a tight connection between psychopathology concepts that are used and the way those concepts are operationalized and defined. In contrast, the use of the same word to mean more than one thing contributes to incoherence, inefficiency, and confusion. In this paper, we review three possible meanings of the word "dimension" as it relates to the assessment of psychopathology and describe how the indiscriminate use of this word has caused confusion in the general context of the transition to a more evidence-based approach to mental health diagnosis. We attempt to disambiguate the term "dimension" by demarcating three concepts that can be distinguished based on different empirical standards: continuous variables, unidimensional dimensions, and distinct dimensions.
Bayes and the Evidence Base: Reanalyzing Trials Using Many Priors Does Not Contribute to Consensus
Authors: Harm-Jan de Grooth, Olaf L. Cremer
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Bayes and the Evidence Base: Re-Analyzing Trials Using Many Priors Does Not Contribute to Consensus." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Solving the Kidney Transplant Conundrum Through Systems Thinking
Authors: L. Ebony Boulware
Journal: JAMA Internal Medicine (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Effect of a Novel Multicomponent Intervention to Improve Patient Access to Kidney Transplant and Living Kidney Donation
Authors: Amit X. Garg, Seychelle Yohanna, Kyla L. Naylor, Susan Q. McKenzie, Istvan Mucsi, Stephanie N. Dixon, Bin Luo, Jessica M. Sontrop, Mary Beaucage, Dmitri Belenko, Candice Coghlan, Rebecca Cooper, Lori Elliott, Leah Getchell, Esti Heale, Vincent Ki, Gihad Nesrallah, Rachel E. Patzer, Justin Presseau, Marian Reich, Darin Treleaven, Carol Wang, Amy D. Waterman, Jeffrey Zaltzman, Peter G. Blake
Journal: JAMA Internal Medicine (2023)

Patients with advanced chronic kidney disease (CKD) have the best chance for a longer and healthier life if they receive a kidney transplant. However, many barriers prevent patients from receiving a transplant.To evaluate the effect of a multicomponent intervention designed to target several barriers that prevent eligible patients from completing key steps toward receiving a kidney transplant.This pragmatic, 2-arm, parallel-group, open-label, registry-based, superiority, cluster randomized clinical trial included all 26 CKD programs in Ontario, Canada, from November 1, 2017, to December 31, 2021. These programs provide care for patients with advanced CKD (patients approaching the need for dialysis or receiving maintenance dialysis).Using stratified, covariate-constrained randomization, allocation of the CKD programs at a 1:1 ratio was used to compare the multicomponent intervention vs usual care for 4.2 years. The intervention had 4 main components, (1) administrative support to establish local quality improvement teams; (2) transplant educational resources; (3) an initiative for transplant recipients and living donors to share stories and experiences; and (4) program-level performance reports and oversight by administrative leaders.The primary outcome was the rate of steps completed toward receiving a kidney transplant. Each patient could complete up to 4 steps: step 1, referred to a transplant center for evaluation; step 2, had a potential living donor contact a transplant center for evaluation; step 3, added to the deceased donor waitlist; and step 4, received a transplant from a living or deceased donor.The 26 CKD programs (13 intervention, 13 usual care) during the trial period included 20 375 potentially transplant-eligible patients with advanced CKD (intervention group [n = 9780 patients], usual-care group [n = 10 595 patients]). Despite evidence of intervention uptake, the step completion rate did not significantly differ between the intervention vs usual-care groups: 5334 vs 5638 steps; 24.8 vs 24.1 steps per 100 patient-years; adjusted hazard ratio, 1.00 (95% CI, 0.87-1.15).This novel multicomponent intervention did not significantly increase the rate of completed steps toward receiving a kidney transplant. Improving access to transplantation remains a global priority that requires substantial effort.ClinicalTrials.gov Identifier: NCT03329521.
Traditional Chinese medicine for the treatment of immune-related nephropathy: A review
Authors: Pu Jiang, Changliang Yao, De-an Guo
Journal: Acta Pharmaceutica Sinica B (2023)

Immune-related nephropathy (IRN) refers to immune-response-mediated glomerulonephritis and is the main cause of end-stage renal failure. The pathogenesis of IRN is not fully understood; therefore, treatment is challenging. Traditional Chinese medicines (TCMs) have potent clinical effects in the treatment of the IRN conditions immunoglobulin A nephropathy, lupus nephropathy, and diabetic nephropathy. The underlying mechanisms mainly include its inhibition of inflammation; improvements to renal interstitial fibrosis, oxidative stress, autophagy, apoptosis; and regulation of immunity. In this review, we summarize the clinical symptoms of the three IRN subtypes and the use of TCM prescriptions, herbs, and bioactive compounds in treating IRN, as well as the potential mechanisms, intending to provide a reference for the future study of TCM as IRN treatments.
Towards overcoming obstacles of type II photodynamic therapy: Endogenous production of light, photosensitizer, and oxygen
Authors: Lin Yu, Zhen Liu, Wei Xu, Kai Jin, Jinliang Liu, Xiaohui Zhu, Yong Zhang, Yihan Wu
Journal: Acta Pharmaceutica Sinica B (2023)

Conventional photodynamic therapy (PDT) approaches face challenges including limited light penetration, low uptake of photosensitizers by tumors, and lack of oxygen in tumor microenvironments. One promising solution is to internally generate light, photosensitizers, and oxygen. This can be accomplished through endogenous production, such as using bioluminescence as an endogenous light source, synthesizing genetically encodable photosensitizers
Oncolytic α-herpesvirus and myeloid-tropic cytomegalovirus cooperatively enhance systemic antitumor responses
Authors: Haifei Jiang, Rebecca Nace, Emily Ariail, Yejun Ma, Erin McGlinch, Coryn Ferguson, Talia Fernandez Carrasco, Nandakumar Packiriswamy, Lianwen Zhang, Kah Whye Peng, Stephen J. Russell
Journal: Molecular Therapy (2023)
The research trends in total mesorectal excision in the past twenty years: A bibliometric analysis (Correspondence)
Authors: Yan-Dong Miao, Wu-Xia Quan, Fang Zhang
Journal: International Journal of Surgery (2023)

aThe Cancer Center, Yantai Affiliated Hospital of Binzhou Medical University, The 2nd Medical College of Binzhou Medical University, Yantai 264000, China bYantai Affiliated Hospital of Binzhou Medical University, The 2nd Medical College of Binzhou Medical University, Yantai 264000, China Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. Published online ■ ■ *Corresponding author. Address: Chief Doctor, Professor, Cancer Center, Yantai Affiliated Hospital of Binzhou Medical University, The 2nd Medical College of Binzhou Medical University, Yantai 264100, China. E-mail address: [email protected] (F. Zhang). *Corresponding author. Address: Cancer Center, Yantai Affiliated Hospital of Binzhou Medical University, The 2nd Medical College of Binzhou Medical University, Yantai 264100, China. E-mail address: [email protected] (Y-D. Miao). This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/